Proteome-wide analysis of Trypanosoma cruzi exponential and stationary growth phases reveals a subcellular compartment-specific regulation

Trypanosoma cruzi, the etiologic agent of Chagas disease, cycles through different life stages characterized by defined molecular traits associated with the proliferative or differentiation state. In particular, T. cruzi epimastigotes are the replicative forms that colonize the intestine of the Triatomine insect vector before entering the stationary phase that is crucial for differentiation into metacyclic trypomastigotes, which are the infective forms of mammalian hosts. The transition from proliferative exponential phase to quiescent stationary phase represents an important step that recapitulates the early molecular events of metacyclogenesis, opening new possibilities for understanding this process. In this study, we report a quantitative shotgun proteomic analysis of the T. cruzi epimastigote in the exponential and stationary growth phases. More than 3000 proteins were detected and quantified, highlighting the regulation of proteins involved in different subcellular compartments. Ribosomal proteins were upregulated in the exponential phase, supporting the higher replication rate of this growth phase. Autophagy-related proteins were upregulated in the stationary growth phase, indicating the onset of the metacyclogenesis process. Moreover, this study reports the regulation of N-terminally acetylated proteins during growth phase transitioning, adding a new layer of regulation to this process. Taken together, this study reports a proteome-wide rewiring during T. cruzi transit from the replicative exponential phase to the stationary growth phase, which is the preparatory phase for differentiation

Differences Between Intact and Ovariectomized Hemiparkinsonian Rats in Response to L-DOPA, Melatonin, and L-DOPA/Melatonin Coadministration on Motor Behavior and Cytological Alterations

Parkinson?s disease (PD) higher incidence has been observed in postmenopausal women compared to premenopausal women, suggesting estrogen neuroprotective effect. L-DOPA (LD) chronic treatment causes dyskinesia; evidences indicate that LD increases the preexisting oxidative stress condition. This study determines melatonin ability, alone or in combination with LD (LD/Mel) to protect dopaminergic loss induced by 6-OHDA in a rat PD model in ovariectomized (OVX) and intact (with ovaries (W/OV)) rats on motor behavior and cytological alterations, comparing with LD-only treated rats. LD/Mel-treated rats showed dyskinesia decrease (score 5–7.5) and had the best performance in the staircase test (five pellets) throughout all studies. The beam walking time was 20–35 s, showing good coordination (as control group (20–38 s)), dopaminergic cells increase of 22.8% (W/OV rats) and 27.2% (OVX rats) in the contralateral side as well as 100% conservation in the contralateral dendritic spines. Our results suggest that LD/Mel co-administration and estrogen presence result in an efficient treatment to reduce dyskinesia through the conservation of some dopaminergic cells, which imply a well-preserved neuropil of a less denervated striatum. We assume that these results are because of a synergistic effect between LD, melatonin and estrogens

Educación Superior y Pandemia. Aprendizajes y buenas prácticas en Iberoamérica

La aportación actual no entra en analizar aspectos generales de la pandemia (naturaleza, origen, extensión general y en el país, etc.) o de otras situaciones que se derivan del confinamiento, por considerar que son suficientemente conocidos. Tampoco pretende realizar una recensión de informes sobre la temática elaborados por organismos como la UNESCO-IESALC, el Banco Mundial, el BID o la CRUE y revisar las aportaciones de investigadores de la temática. Más bien trata de aportar concreciones y dimensiones prácticas de la Educación Superior de cada país que puedan ayudar en los aspectos de organización y gestión de estas instituciones. En este sentido considera aspectos referidos a: (1) Desarrollo de las enseñanzas: alteraciones en la duración y estructura de los títulos; modificaciones de objetivos, metodologías y sistemas de evaluación; atención a colectivos vulnerables; etc.(2) Organización institucional: atención a las personas (gestión del alumnado, profesorado y personal de administración y servicios, rol de los directivos, etc.); infraestructuras; desarrollo de procesos (matriculación, gestión administrativa y económica, etc.); y resultados (académicos como tasa de aprobados, nivel de abandono u otros; y no académicos). (3) Vinculación con el entorno: actuaciones de y con la comunidad o colaboraciones significativas. Incluye el escrito de cada país con referencias y reflexiones sobre los anteriores aspectos, así como algunas experiencias de interés y, por último, reflexiones, valoraciones y retos sobre la gestión en los momentos de confinamiento y reapertura, con la idea de identificar aprendizajes significativos y orientaciones de cara a la actuación en la situación actual y similares que se puedan producir en el futuro. Las diferentes aportaciones se centran en la enseñanza universitaria, incluyendo los estudios superiores, que en muchos países tienen gran importancia y desarrollo, y tratan de proporcionar una visión general de los diferentes países sin obviar descender a las particularidades concretas que exigen el identificar buenas prácticas o medidas específicas de organización y desarrollo de la formación. Hablamos del trabajo de 41 especialistas de 13países iberoamericanos que permiten conocer y analizar las actuaciones por países, pero también realizar un estudio de las iniciativas que se han tomado en todos los países considerando algunos de los tópicos que considera el Informe. En todo caso, cabe destacar la actualidad y trascendencia del tema y la rapidez por trasladar a la sociedad un Informe detallado sobre las actuaciones universitarias existentes y sus resultados

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Acute Effect of Exogenous Melatonin on Cognitive Functions in Young Adults Consuming Alcohol

La melatonina es una neurohormona asociada con los ciclos del sueño y como barredor de radicales libres. Recientemente, se ha demostrado que es eficaz para proteger el hipocampo en condiciones de estrés oxidativo, reduciendo el daño celular y promoviendo mejores ejecuciones en las pruebas de memoria. En este estudio, se evaluó si el consumo diario de 10 mg de melatonina podría tener efectos favorables sobre la memoria y el pensamiento abstracto en adultos jóvenes que consumían alcohol. Los participantes fueron evaluados con las pruebas de Memory span y con la prueba de tarjetas de Wisconsin. Los resultados mostraron que el consumo exógeno de melatonina se asoció con una mejora significativa en funciones cognitivas, aun en condiciones de consumo regular de alcohol.Melatonin is a neurohormone associated with sleep cycles and free radical scavenger. Recently, it has been shown to be effective in protecting the hippocampus under stress conditions, reducing cell damage and promoting better executions in memory tests. In this study, it was tested whether the daily consumption of 10 mg of melatonin could have favorable effects on memory and abstract thinking in adults who consumed alcohol. The participants were evaluated with the "Memory Span" and Wisconsin cards test, The results showed that exogenous melatonin consumption was associated with a significant improvement in cognitive functions, even when alcohol is consumed regularl